PB1833: FUNCTIONAL POLYMORPHISMS OF TLR2-4 &amp; C2 DO NOT PLAY A CRUCIAL ROLE IN INCIDENCE OF INFECTIONS IN A GREEK COHORT OF PATIENTS WITH ACUTE MYELOID LEUKEMIA.
Authors: C. Papadopoulos, G. Tsinti, S. Matthaios, P. Euthimia, D. Katerina, N. Giannakoulas
Journal: HemaSphere (2022)

Background: Patients with Acute Myeloid Leukemia (AML) display long periods of neutropenia due to marrow failure and chemotherapy, which make them particularly susceptible to infections from a wide range of pathogens. The incidence of infections in AML patients under treatment may also delay subsequent treatments and also increases the morbidity and mortality rates. Innate immune system is the first line of defense against microbial pathogens, while at the same time it is the orchestrator of adaptive immunity. Disorders in the major molecules of innate immunity such as Toll Like Receptors (TLRs) or in individual components of other system such as the complement, might be aggravating factors for the already immune-compromised patient. The role of common functional innate immunology genes in the incidence in patients with AML remains unclear as previous studies provide conflict results. Aims: In the present study, the scientific question was whether the D299G (rs4986790) & T299I(rs4986791) polymorphisms of the TLR4 gene, the R753Q (rs57443708) polymorphism of the TLR2 gene, and the most common deletion of the C2 (rs9332736) gene are prognostic factors for the development of microbial infections in 107 AML Caucasian patients from Greece. Methods: I) Clinical data (type of infections, survival, etc.) of 107 patients with AML (73 males, 34 females, 68 mean age) were recorded. All patients or their families had given consent for their genetic material processing and analysis. The isolated pathogens were separated into four groups (Table 1B) (Gram-Positive Bacteria, Gram-Negative Bacteria, Fungi and Clamydia). II) The sample type consisted of peripheral blood and bone marrow. For DNA extraction PureLink®Genomic DNA kit (Qiagen & Invitrogen) was used. III) Genetic polymorphisms TLR4(D299G, rs4986790), TLR4(T399I, rs4986791), TLR2(R758Q, rs57443708) and C2(rs9332736, C2-c.841_849 + 19del28) detection, was performed as previously described in detail (Johnson et al., 1992; Liadaki et al., 2011). IV) For the comparison of our cohort’s genotype frequency with the genotype frequency of worldwide population, was used gnomAD database. V) The results assessed with Fisher Exact test. Statistical significance level was 0.05. Statistical analysis was performed with SPSS 2017. Results: The results of molecular detection are described on Table 1A. None statistical significant were observed between polymorphisms of immune genes (TLR2, TLR4, C2) and the frequency of appearance of isolated infectious agents (P-value > 0,05). Image:Summary/Conclusion: As mentioned above, there are conflicting results in the literature considering the role of the analyzed polymorphisms in the incidence of infections and sepsis in patients with AML. In our study, our patients did not have any statistically significance between polymorphisms (TLR2, TLR4 and C2) and underlined infections. Further studies and also meta-analysis of all related published studies are necessary in order to provide conclusive remarks.